The matrix metalloproteinases (MMPs) include a family of structurally similar zinc-dependent enzymes that degrade all of the major components of the extracellular matrix. MMPs include the collagenases, gelatinases A and B, the stromelysins, matrilysin, metalloelastase, and the membrane-type matrix metalloproteinases. Over-expression and activation of MMPs have been linked to development of several diseases, such as arthritis, cancer, and multiple sclerosis. Although MMPs classically have been implicated in basement membrane destruction associated with late-stage tumor cell invasion and metastasis, one MMP member, matrilysin, has recently been shown to be expressed in early stage human colorectal tumors. (C. L. Wilson et al., Proc. Natl. Acad. Sci. USA 94:1402-1407 (February 1997)). Expression of MMPs in human chondrosarcoma cells has been reported. Soderstrom et al. (2001) APMIS 109:305-15; Kerkela et al. (2001) Bone 29:487-93; Sakamoto et al. (1999) J. Cancer Res. Clin. Oncol. 125:541-48.
Chondrosarcoma usually occurs in late adulthood or old age, and is the second most common form of bone malignancy. Conventional chondrosarcoma tumors are graded from stage I through stage III, with stage III being the most advanced. In addition to conventional chondrosarcoma, there are other types of chondrosarcoma with distinguishing characteristics: myxoid, mesenchymal, clear cell, and dedifferentiated (spindle cell) chondrosarcoma.
Consequently, a need exists for agents that can inhibit the growth and spread of chondrosarcoma cells.